The proposed work deals with two major areas of investigation. The first is an evaluation of the factors which regulate insulin binding, action, and degradation in isolated hepatocytes. These studies are concerned with various metabolic parameters in the liver including lipid synthesis, glycogen synthesis, glucose oxidation, and amino acid transport, and the ability of insulin to regulate these responses in hepatocytes from control, fasted, diabetic, aged, and obese rats. These studies are performed in freshly isolated and primary cultures of hepatocytes in the presence of defined incubation conditions. The factors regulating these metabolic parameters can be evaluated. Additional studies deal with the mechanisms by which insulin regulates its degradation and the member of insulin receptors in primary cultures of hepatocytes. The relationship between insulin binding and degradation is also under investigation. The second major area of investigation is concerned with the factors which regulate hexose uptake in adipocytes, including membrane fluidity. Studies in progress will assess the regulation of basal and insulin stimulated sugar uptake, the physical characteristics of these two systems, and the mechanisms by which insulin stimulates sugar uptake.